Sex-specific behavioral alterations and underlying molecular mechanisms of zebrafish with environmental-related zinc exposure

Human activities give rise to plenty of environmental zinc accumulation which leads to various health problems in many kinds of organisms. Deleterious effects of zinc contamination on zebrafish have been reported, however, studies associated with sex-specific neurobehavior phenotypes and physiological mechanisms are limited. The present study investigated behavioral and physiological divergence between male and female zebrafish exposure to environment-related zinc chloride (1.0 or 1.5 mg/L). Our results showed that zinc exposure exerted neurobehavior toxicity in a sex-specific manner and altered behavioral dimorphism in zebrafish. Furthermore, we confirmed that zinc exposure dysregulated brain reproduction functions and ion homeostasis, intestinal immunomodulation and neurotransmitter signatures, and hepatic RNA metabolism in a sex-specific manner. Zinc accumulation results in physiological dyshomeostasis of the gut-liver-brain axis, thereby leading to neurodegeneration-like behaviors. Differences in reproductive system, endocrine system and energy regulation system between two sexes might be partly responsible for sex-dependent responses. Female zebrafish have higher metabolic rates and more active immune systems, which may increase their susceptibility to environmental stressors like zinc. Our study emphasized sex-dependent behavioral alterations and the molecular mechanisms of zinc exposure, thus providing new insight into assessment of the sex-specific effects of environment pollutant on animal behavior and physiology in aquatic ecosystems.